This project investigates cell cycle regulation in proliferating, quiescent, and differentiating lens cells through studies of proto-oncogenes, cyclins, and cyclin- dependent kinases. We have found that cyclin B/p34cdc2, a complex normally associated with mitosis, is present in postmitotic lens fiber cells and possesses kinase activity. Transgenic animals are being used to test the hypothesis that cyclin B/p34cdc2 may play a role in chromatin condensation and denucleation of differentiating lens fiber cells. Related studies seek to determine how the normally tight coupling of cyclin B expression and DNA replication is overridden during fiber cell differentiation. A second area of intense study is the regulation of proto-oncogene expression and cell proliferation in lens epithelial cells by 12(S)HETE, a lipoxygenase metabolite of arachidonic acid. We have demonstrated that 12(S)HETE plays an essential role int he proliferative response to epidermal growth factor (EGF) and insulin in both rat and human lens epithelial cells. The mechanism of this effect is under investigation, and the potential of lipoxygenase inhibitors for contolling lens epithelial cell proliferation during posterior capsule opacification is being evaluated.